This proposal will study the significance of the recently-discovered daily rhythm in cerebrospinal fluid (CSF) concentrations of the posterior pituitary hormone, arginine vasopressin. This will be addressed by delineating the rhythm's characteristics, regulation, neural site of origin, and possible physiological role. We will use our recently developed techniques for chronic, continuous or serial CSF withdrawal in undisturbed, freely-moving cats and rats. Vasopressin concentrations will be measured in bodily fluids by radioimmunoassay. The proposed studies for the first two grant years will build a foundation of basic information regarding the characteristics and regulation of the CSF vasopressin rhythm. First, in the cat the characteristics of the rhythm will be examined in order to show that the CSF vasopressin rhythm is due to rhythmic release of the peptide directly into CSF. Second, in the cat and rat we will demonstrate the circadian nature and regulation ofthe CSF rhythm. This aspect of the study will include determination of te effects of ablation of a putative biological clock located in the suprachiasmatic nuclei on the circadian expression of te CSF vasopressin rhythm. Third, in the cat we will show that the circadian regulation of the CSF rhythm is effectively insulated from the osmotic regulation of blood vasopressin. The proposed studies for the third grant year will use this acquired information to begin to investigate the neural site of origin and possible physiological role o the CSF vasopressin rhythm. First, if ablation of the suprachiasmatic nuclei disrupts the CSF rhythm, we will examine whether the nuclei rhythmically secrete the peptide into CSF by transplanting fetal hypothalamic tissue into rats with suprachiasmatic nuclei lesions. Finally, we will demonstrate in our laboratory that circadian processes influence retention performance in rats. This will provide the necessary information for future studies designed to examine the role of the rhythm in vasopressin in CSF on the rhythmic fluctuations of memory. The results of htese studies will provide new insights into how peptide hormones modulate complex behavioral processes in the brain.